1. Field of the Invention
The present invention relates generally to implants for use in repairing various portions of the mammalian skeletal system and, more particularly, to implants for use in clinical procedures such as bone fracture repair, regeneration of bone loss, augmentation of deficient bone, and related procedures.
2. Description of Related Art
Various types of defects in the mammalian skeletal system can be treated by various surgical procedures. Defects in the mammalian skeletal system may include bone fracture, loss of bone occurring from traumatic, surgical, or infectious sources, and bone deficiencies stemming from conditions such as atrophy and congenital anomalies.
One procedure that is common in the prior art for treating bone defects involves the placement of additional bone into the bone defect area. This procedure, which is commonly referred to as bone grafting, is the second most frequently performed surgical grafting procedure, with skin grafting the most common surgical grafting procedure. Current bone grafting procedures include the use of vascularized or non-vascularized autografts and allografts.
A bone autograft is a portion of bone taken from another area of the skeletal system of the patient. A bone allograft, in contrast, involves a human donor source other than the recipient patient. Allogenic bone graft typically comprises bone harvested from cadavers, which is subsequently treated and stored in a bone bank and ultimately used as a bone graft implant. Allogenic bone graft is known to have osteoconductive and osteoinductive capabilities, although the osteoinductive properties are limited because of the necessary tissue sterilizing and cleaning procedures associated with harvesting these bone grafts. The term osteoconduction refers to a class of biomaterials which provide a three-dimensional porous framework to conduct the ingrowth of new living bone into this structure. The term osteoinduction refers to a class of materials having capabilities of recruiting mesenchymal stem cells of the patient and promoting their differentiation into osteoblasts, which are bone forming cells. An osteoinductive material will typically form bone if implanted into an area where bone would not normally grow. For example, the placement of bone morphogenic proteins into the muscle of a patient will result in ectopic (outside of bone) bone formation.
Both bone autografting procedures and bone allografting procedures are associated with shortcomings in the healing of bone defects within the mammalian skeletal system. Bone autografting procedures are typically associated with limitation of donor sites, bone quantity, and donor site morbidity (especially if multiple donor sites are required). Bone allografting procedures, to begin with, only have limited osteoinductive capabilities. In addition to the very limited osteoinduction properties of allogenic bone grafts, compared to autograft samples, allografts are immunogenic to a certain degree, bear the risk of disease transmission (e.g. HIV and Hepatitis), and, depending on the size of the allograft, require a long time for ingrowth and partial substitution with new bone. This long substitution process often requires a time duration of greater than one year before satisfactory clinical results are obtained. Additionally, pressure from the adjacent musculature may dislocate bone graft material. Bone grafts may re-fracture after fixator removal if bone ingrowth and substitution is inadequate.
As a substitute to actual bone grafts, which include autografts and allografts, various bone graft substitutes have been used by the prior art for treating bone defects in the mammalian skeletal system.
Porous ceramic bone graft substitutes, for instance, such as coralline hydroxyapatites, operate similarly to bone grafts by providing a three-dimensional structural framework. This framework conducts the regenerating bone of the patient into the porous matrix of the three-dimensional structural framework. This process of conducting the regenerating bone into the porous matrix is commonly referred to as osteoconduction, as opposed to osteoinduction discussed above. Permanent, non-resorbable, inorganic, ceramic implants have shortcomings such as inherent brittleness and large framework volume fractions. The framework volume fraction of a typical bone graft substitute comprises approximately 40 percent of the volume where new bone could otherwise grow. This 40 percent volume occupied by a bone graft substitute, consequently, cannot be occupied by the regenerating bone of the patient.
A process referred to as guided tissue regeneration is widely used by periodontists to regenerate bone and periodontal ligaments (ligaments between the tooth root and the bone) around dental implants, for example. This surgical procedure uses cell-occlusive (cells cannot pass through) but fluid-permeable membranes, which are otherwise known as semipermeable membranes, in order to cover and segregate a bone defect from the surrounding soft tissues. U.S. Pat. No. 3,962,153 discloses such a cell-occlusive, fluid-permeable membrane. Use of these cell-occlusive, fluid permeable membranes, has been predominantly developed and used by periodontists over the last decade, who worked in the mouth around teeth. The human body has many tissue types which originate from three primary germ layers of the embryo: the ectoderm, the mesoderm and the entoderm. From the ectoderm are derived the skin and its attached tissues, such as nails, hair and glands of the skin, the nervous system, external sense organs and the epithelial lining of the mouth and anus. From the mesoderm are derived the connective tissues, bone, cartilage, muscle, blood and blood vessels. From the entoderm are derived, among others, the digestive tract, bladder and urethra. The xe2x80x9cprecursorxe2x80x9d cells of these layers are limited to only becoming cells of their respective tissue type. Bone, muscle, connective tissue, blood vessels and cartilage are of mesenchymal origin which means from the meshwork of embryonic connective tissue in the mesoderm, and are formed from versatile mesenchymal stem cells, whereas the lining of the mouth is of ectodermal origin and is formed of epithelial cells derived from the ectoderm. Ectodermal cells do not have the potential to become bone forming cells and, conversely, mesenchymal cells do not have the potential to form epithelium.
Epithelial cells are present in the mouth, but are not present in many other areas of the mammalian skeletal system, such as areas near long bones of the mammalian skeleton. The development of cell-occlusive, fluid permeable membranes was developed in the context of periodontal and oral applications, for the purpose of excluding the introduction of epithelial cells into the bone defect area of the patient because they are believed to hinder bone formation. Epithelial cells proliferate faster than bone cells and, therefore, the exclusion of these epithelial cells from the bone defect area has been considered to be essential for optimal bone and ligament regeneration in these periodontal and oral applications. Although cell-occlusive, fluid permeable membranes have been predominantly used in periodontal and oral applications, these cell-occlusive membranes have recently also been applied for tissue segregation in other defect sites in the mammalian skeletal system, such as long bone defects.
These cell-occlusive membranes of the prior art have a shortcoming of blocking blood vessels and mesenchymal cells from entering into the bone defect area. Thus, the advantage of precluding epithelial cells from the bone defect area in the oral cavity is achieved at the expense of also precluding entry of blood vessels and surrounding mesenchymal cells into the bone defect area, as well. In periodontal and oral applications, the advantage of precluding epithelial cells is believed to be worth the shortcoming of also precluding blood vessels and surrounding mesenchymal cells from the bone defect area. In other areas of the mammalian skeletal system, however, where epithelial cells are not present, these cell-occlusive, fluid-permeable membranes preclude the introduction of blood vessels and surrounding mesenchymal cells for no apparent reason. Thus, a need has existed in the prior art for a cell-permeable membrane barrier to protect non-periodontal bone defects from gross soft tissue prolapse and to thereby facilitate bone regeneration.
Turning to FIG. 1, a typical cell-occlusive fluid permeable membrane 10 is illustrated surrounding a first section of the long bone 12 and a second section of long bone 14. The bone defect area 20 is bounded by the two ends 16, 18 of the first section of long bone 12 and the second section of long bone 14, respectively, and by the cell-occlusive, fluid-permeable membrane 10. Although this bone defect area 20 can receive blood from the bone vessels 23, blood and cells from the surrounding blood vessels 25 and tissues 27 is precluded from entering the bone defect area 20. The periosteum 31 and the surrounding tissues 27 are just external to the cell-occlusive, fluid-permeable membrane 10 and are guided in the directions of the arrows Al and A2.
In addition to being cell-occlusive, the cell-occlusive, fluid permeable membrane 10 suffers from a lack of rigidity, as evidenced by the hour-glass configuration of the cell-occlusive, fluid-permeable membrane 10 in FIG. 1. A typical thickness of the cell-occlusive, fluid-permeable membrane 10 comprises less than 5 microns. Since periodontal defects are typically small, and since oral soft tissues typically do not apply much pressure, the cell-occlusive, fluid-permeable membrane 10 of the prior art has maintained its very thin and flexible configuration. Unfortunately, this very thin and flexible configuration, which is somewhat suitable for periodontal and oral applications, is not suitable for maintaining and protecting a sufficiently large bone defect area 20 in non-periodontal and non-oral applications. Since muscles are much larger and more powerful in orthopedic applications, for example, the cell-occlusive, fluid-permeable membrane 10 cannot provide sufficient protection against the prolapse of soft tissues into the bone defect area 20. When the surrounding tissues prolapse into the bone defect area 20, these interposed tissues present a physical barrier for the regenerating bone. The regenerating bone will not be able to push the interposed soft tissues out of the bone defect area, and subsequently, further regeneration of the bone in these areas occupied by the prolapsed soft tissues is prevented. A xe2x80x9cnon-unionxe2x80x9d (or pseudoarthrosis which means pseudo-joint) may result, comprising fibrous scar tissue instead of bone. Additionally, the prior art cell-occlusive, fluid-permeable membrane 10 is non-resorbable, and cannot be absorbed by the patient""s body. Consequently, in order to avoid the risk of bacterial infection, the cell-occlusive, fluid-permeable membrane 10 must be removed during a subsequent operation, which may introduce further complications and risks to the patient. Thus, in addition to being cell-occlusive, prior membranes suffer from lack of inherent strength and non-resorbability.
A few other devices have been developed in the prior art for treating bone defects, but these devices comprise either fixation devices or prosthetic devices. A fixation device, comprising a titanium screen mesh, is disclosed in U.S. Pat. No. 5,346,492. This titanium screen mesh forms a fixation device, which is designed to be non-resorbable. The fixation device comprises a metallic plate structure which provides the necessary strength, at the cost of being non-resorbable. To date, any known resorbable material would not be capable of providing the equivalent rigidity and function of the titanium mesh screen. The metallic plate structure of the fixation device comprises a number of perforations designed specifically for accommodating screws for fixation. These screw perforations have diameters (between 4.8 millimeters and 17.5 millimeters), which do not prevent gross prolapse of soft tissues into the bone defect area such gross prolapse of soft tissues occupies space which would otherwise be filled with new bone. The physical barrier presented by the prolapsing soft tissues greatly impairs new bone formation within the bone defect area. The fixation device is secured onto the bone of the patient with the screws and is designed to be permanently left inside the patient. Any proliferation of blood vessels through these screw holes would be destroyed by any subsequent removal of the fixation device. On the other hand, if the fixation device is left in permanently, which is a disclosed embodiment, the bone of the patient will be permanently stress shielded. In other words, the mended bone, after initial healing will subsequently start to resorb, since this new bone is not exposed to functional (mechanical) stress. The fixation device, if left in the patient, will shield the bone defect area from functional stress and thus prevent an optimal amount of new bone formation.
A prosthetic device, which comprises holes punched into a planar material for facilitating suturing of the prosthetic device, is disclosed in U.S. Pat. No. 5,222,987. This prosthetic device, however, is only disclosed in the context of fabricating artificial bone structure. In other words, this prosthetic device is not used in any process associated with bone regeneration. The prosthetic device comprises a fabric-like composite onto which a polymer or resin is added, before the resulting product is molded into the shape of a bone. A polymerizable initiator is subsequently added to harden and bond the materials together. Small holes or ports may be added to accommodate sutures for attaching the prosthetic device to the body. The prosthetic device is specifically designed as a replacement for the rib cage of a mammalian skeletal system, and does not facilitate bone regeneration.
Other porous devices, in addition to the above-mentioned fixation and prosthetic devices, have been implemented by the prior art. One such device, which is disclosed in U.S. Pat. Nos. 5,306,304, 5,464,439, and 4,932,973, disclose an allogenic bone graft membrane having pores therein. The allogenic bone graft membrane is disclosed in these patents as providing a filler for bone defects. The matrix-like properties of the allogenic bone graft provide osteoconduction, and the morphogenic proteins within the allogenic bone graft provide osteoinductive properties. As mentioned before, an allogenic bone graft is typically harvested from a human cadaver and subsequently processed for implantation. The allogenic bone graft is intended to become integrated with the new bone of a patient and partially remodeled over time into a composite of both cadaver bone and new regenerated natural bone, while permanently remaining within the bone defect area of the patient. The pores in the allogenic bone graft membrane of these patents are designed to maximize the exposed surface area in order to enhance its osteoinductive contribution, as bone morphogenic proteins are released from the surface of the allogenic bone graft. This allogenic bone graft matrix will never be completely resorbed. This is obviously disadvantageous, because its structure reduces the space for new bone regeneration.
Another device, which comprises apertures or pores for facilitating tissue growth therein, is disclosed in U.S. Pat. No. 5,326,356. This patent is directed to an apparatus for generating artificial skin grafts. Bio-compatible membranes comprising natural, synthetic, or semi-synthetic origin are used as a support for the in vitro (outside of a living organism) growth of epithelial skin cells. These epithelial skin cells are grown into the pores of the membrane outside of the body of the patient. The resulting artificial skin graft is obviously not intended for use on the mammalian skeletal system. This artificial skin graft, in any event, would be far too thin and flexible for use on the mammalian skeletal system, and further would not have adequate fixation strength. Moreover, the epithelial cells which comprise the artificial skin graft are not present in the non-periodontal and non-oral applications, such as long bones, where a cell-permeable membrane is needed in the prior art for facilitating bone regeneration.
The present invention recognizes that a cell-occlusive, fluid permeable membrane is not suitable for bone regeneration in non-periodontal and non-oral applications. In addition to lacking rigidity and resorbability, the present invention recognizes that these prior art cell-occlusive, fluid-permeable membranes hinder bone regeneration by blocking the ingress of blood vessels and cells into the bone defect area. The protective bone regeneration membrane of the present invention has a much smaller net surface area, compared to prior art cell-occlusive, fluid permeable membranes, resulting from the introduction of cell-permeable apertures into the membrane of the present invention. In addition to having a smaller net surface area, the protective bone regeneration membrane of the present invention is substantially stronger and more rigid than prior art cell-occlusive, fluid permeable membranes.
According to one aspect of the present invention, an implant for protecting biological tissue defects from a prolapse of adjacent soft tissues during in vivo repair of the biological tissue defects includes a substantially planar sheet of non-metallic base material. The implant further includes a plurality of apertures disposed in the substantially planar sheet of non-metallic base material. The apertures are adapted for allowing a proliferation of vasculature and connective tissue cells, derived from the adjacent soft tissues, into the biological tissue defect, while preventing any gross prolapse of the adjacent soft tissues into the biological tissue defect. The connective tissue cells include mesenchymal cells, and the implant may be impregnated with at least one substance for cellular control. This substance for cellular control may include at least one of a chemotactic substance for influencing cell-migration, an inhibitory substance for influencing cell-migration, a mitogenic growth factor for influencing cell proliferation, a growth factor for influencing cell differentiation, and factors which promote neoangiogenesis (formation of new blood vessels). The biological tissue defect preferably comprises a bone defect and, more preferably, comprises a non-periodontal, non-oral bone defect.
The implant may be used in combination with a fixation device for stabilizing the bone defect. The material of the implant is flexible enough to conform to a curvature of a bone and strong enough to reduce macro-motion of the bone defect and limit transmission of surrounding motion into the interior space when the fixation device is attached to the bone defect. The implant is adapted for protecting the bone defect from a prolapse of adjacent soft tissues into the bone defect during repair of the bone defect and, further, is adapted for preventing stress shielded resorption of bone after the repair of the bone defect. The bone, which is prevented from being resorbed, may include either an autograft, an allograft, and/or new regenerated bone within the bone defect.
According to another aspect of the present invention, the implant is resorbable. The resorption of the implant, according to the present invention, can prevent stress shielding of the bone defect, to thereby prevent resorption of new bone which would occur if the bone defect were stress shielded by either the fixation device or the implant, or both. The fixation device may be resorbable or non-resorbable. When the fixation device is resorbable, the fixation device loses its mechanical strength within 24 months and, more preferably, within 4 to 12 months. This loss of mechanical strength of the fixation device can prevent resorption of new bone near the bone defect which would occur if the bone defect were stress shielded by either the fixation device, the implant, or both. If the fixation device is non-resorbable, according to the present invention, the resorption of the implant can reduce stress shielding of the bone defect area to thereby minimize resorption of new bone near the bone defect. As another option, the implant may be non-resorbable, but flexible enough to prevent stress shielding of the bone defect after the resorbable fixation device has lost its mechanical strength.
Each of the apertures within the implant has a diameter in a range between 20 microns and 3000 microns, and, preferably, has a diameter of approximately 1500 microns. The implant has a thickness in a range between 100 microns and 2000 microns, but may also be configured as thin as 10 microns. This implant comprises at least one of a biodegradable synthetic material and a biodegradable natural material, that is also a non-osteogenic, non-metallic substance having a stiffness sufficient to prevent gross soft tissue prolapse into an area of the bone defect where new bone ideally would grow.
According to one aspect of the present invention, a planar membrane is provided for preventing soft tissue from prolapsing into a protected area of a bone defect. The planar membrane is adapted for being placed outside of the bone defect area, as opposed to being placed within the bone defect area where new bone would ideally grow, to thereby facilitate entirely new bone growth only within the protected area. The planar membrane includes a plurality of apertures disposed therein. Each of the plurality of apertures is adapted for allowing a proliferation of vasculature and connective tissue cells into the protected area, while preventing a prolapse of adjacent soft tissues into the protected area. The planar membrane is adapted for resorption into the body of a patient, within a period of approximately 24 months from an initial implantation of the planar membrane into the body of the patient.
According to another aspect of the present invention, a resorbable membrane is provided for facilitating protected bone regeneration. The resorbable membrane is adapted for being wrapped around the bone defect area, to thereby cover and surround the entire bone defect area and to overlap adjacent areas of bone near the bone defect area. The resorbable membrane has a strength sufficient to prevent prolapse of adjacent soft tissues into the bone defect area and to thereby facilitate bone regeneration independently, without any aid from a fixation device, when the resorbable membrane is secured around the bone defect area and secured to the adjacent areas of bone near the bone defect area. The resorbable membrane forms a tube surrounding the entire bone defect area and overlapping the adjacent areas of bone near the bone defect area, when the resorbable membrane is secured both around the bone defect area and to the adjacent areas of bone near the bone defect area. The resorbable membrane can be frictionally secured around the bone defect area, or can be secured around the bone defect area using at least one of clamps, staples, screws, sutures, and tacks. The fixation device can include at least one of a plate, a screw, an intramedullary rod, and an external fixation device.
According to yet another aspect of the present invention, a method of protecting a biological tissue defect area from soft tissue interposition is provided. The method includes a step of placing a resorbable membrane outside of a boundary of the biological tissue defect, where the resorbable membrane comprises a plurality of apertures adapted for allowing a proliferation of vasculature and connective tissue cells therethrough, while preventing the prolapse of adjacent soft tissues into the biological tissue defect. The biological tissue defect area can include a bone defect area, and the step of placing a resorbable membrane outside of the boundary of the bone defect area can include a step of wrapping the resorbable membrane around two ends of a long bone to thereby surround a void between the two ends of the long bone. A rigid fixation device can subsequently be secured between the two ends of the long bone.